Walking and Dietary Modification for Women With Consecutive Early Miscarriages: a Randomized Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 480
- 试验地点
- 2
- 主要终点
- Take-home Baby Rate
研究概览
简要总结
This study is part of a big one aiming to evaluate how lifestyle interventions during pregnancy affect obstetric results, neonatal metabolism and the intelligence of the offspring (study not yet completed). Data regarding obstetric and neonatal results were entered in NCT01409382, but we decided to split results in two for the sake of clarity.
A cohort of women with early pregnancy losses without antiphospholipid antibodies was selected for two reasons. One is that these women follow strictly the recommendadtions. The second is that no medication has been shown to increase the rate of take-home babies in women with early miscarriages who test negative for antiphospholipid antibodies. We decided to focus on the fibrinolytic system because trophoblast migration and placental vasculogenesis and angiogenesis depend on plasmin-dependent extracellular matrix remodeling. Plasminogen activator inhibitor (PAI)-1 inhibits the generation of plasmin. Since both glucose and insulin increase PAI-1 synthesis, hyperglycemia itself, or by stimulating insulin production, reduces plasmin generation, which may impair placentation.
Abnormalities in glucose metabolism may be also deleterious to embryos by causing epigenetic changes. Chromosomal abnormalities are considered an important cause of early pregnancy losses.
Several lines of evidence lend support to the hypothesis that carbohydrate metabolism abnormalities contribute to the pathogenesis of recurrent early pregnancy losses. One is that of the pregnancies of the women with polycystic ovary syndrome, around 30 and 50% end with first-trimester miscarriages. Hyperinsulinemia is a prevalent feature of the syndrome, and interventions proven effective in reducing insulin levels, such as metformin, have been shown to reduce the rate of early miscarriages. The other is that patients with body mass index of ≥25 kg/m2 have significantly higher odds of early miscarriage, regardless of the method of conception.
The investigator's hypothesis was that a balanced diet combined to regular exercise, by improving glucose homeostasis, would increase the take-home baby rate in women with consecutive early miscarriages. Moderate exercises are usually well tolerated not only by the mother, but also by the fetus, as indicated by tests of fetal well-being, including umbilical artery systolic to diastolic ratio.
详细描述
Women aged 18 to 40 years trying to conceive spontaneously were eligible if they had two or more consecutive pregnancy losses in the first trimester, documented by pathology or ultrasound-confirmed gestational sac.
All participants underwent ultrasound examination before inclusion in the study. Exclusion criteria were any of the following: anatomic anomalies that may increase the risk of pregnancy losses, not amenable to surgical correction during pregnancy, such as uterine septum; antiphospholipid antibodies; prior second- or third-trimester losses; current multiple gestation; disabilities such as hemiplegia or paraplegia; renal or liver failure; conditions requiring a priori anticoagulation.
Participants were enrolled by staff at the participating center. Randomization to the intervention protocol Walking and Diet (W&D) or to a control group was performed before pregnancy occurred by a statistician using a computer-generated random-number table. This was not a double blind study, but care was taken to ensure that appointments of the patients assigned to the intervention protocol did not coincide with those of controls.
The intervention was standardized by training of research staff. Women assigned to W&D were instructed to walk at a moderate pace (4 km/h) for at least 40 minutes, seven days a week. Besides, those who remained seated most of the day were advised to walk 25 to 30 minutes twice a day, avoiding hence more than 12 hours of physical inactivity. Walking could be replaced by stationary bicycle rides or swimming when convenient, which often occurred near term and when the mother was obese. Strenuous exercises were discouraged.
Patients assigned to protocol W&D were also informed of the importance of a balanced diet and recommended to avoid high-glycemic index meals (high-carbohydrate, low-fiber). Sucralose could be used as a sweetener. As a strategy to promote satiety and reduce carbohydrate intake, W&D participants were also advised to eat at least two daily servings of protein-rich food. The intervention began when participants wished to conceive, continuing until delivery. Careful instructions about walking speed and diet were given to participants assigned to W&D at enrolment and at each consultation. During exercise, neither fetal nor maternal cardiac rate were assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
Participants were not blinded, but visits of the two groups were scheduled so as to not coincide..
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •≥ 2 consecutive pregnancy losses in the first trimester;
- •losses should be documented by pathology or ultrasound-confirmed gestational sac.
排除标准
- •(any of the following):
- •anatomic anomalies that may increase the risk of pregnancy losses, not amenable to surgical correction during pregnancy, such as uterine septum;
- •antiphospholipid antibodies;
- •prior second- or third-trimester losses;
- •current multiple gestation;
- •disabilities such as hemiplegia or paraplegia;
- •renal or liver failure;
- •conditions requiring a priori anticoagulation
结局指标
主要结局
Take-home Baby Rate
时间窗: End of pregnancy
次要结局
- Excessive Weight Gain(End of term pregnancies)
- Babies Born at Term(End of pregnancy)
- Mothers Who Used Heparin for Nephrotic Range Proteinuria or Placental Insufficiency(End of pregnancy)
- First-trimester Losses(14 weeks of gestation)
- Live-born Children(End of pregnancy)
- Neonates With Hypoglycemia(One, two and fours hours after birth)
- Appropriate-for-gestational Age Babies(End of pregnancy)
- Gestational Diabetes Mellitus(Pregnancies reaching 24 weeks' gestation)
- Preeclampsia(Pregnancies reaching 20 weeks' gestation)
- Second and Third-trimester Losses(28 weeks of gestation and end of gestation)
研究者
Silvia Hoirisch Clapauch
Principal Investigator
Hospital dos Servidores do Estado do Rio de Janeiro